title: Heparin, carboxyl-reduced sulfated heparin, and Trestatin A sulfate. Antiproliferative and anticoagulant activities.
abstract: Human smooth muscle cells were used to investigate the antiproliferative activities of sulfated carbohydrates. The antiproliferative potencies of coarse heparin fractions prepared by ultrafiltration increased with the mean molecular-weight, whereas the anticoagulant activities of a high-molecular-weight fraction had submaximal values. Furthermore, the dependence of antiproliferative activity on sulfate content is discussed. Carboxyl-reduction of heparin abolished both antiproliferative and anticoagulant activities. Sulfation of this compound yielded CRS-heparin with restored antiproliferative potency but devoid of antithrombin III-mediated anticoagulant activity. Sulfation of the pseudo-nonasaccharide, Trestatin A, yielded a compound having the highest antiproliferative activity, so far observed for a low-molecular-weight compound, and having only weak anticoagulant properties.
authors.affiliation: Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: H P
authors.initials: HP
authors.lastname: Wessel
authors.forename: M
authors.initials: M
authors.lastname: Hosang
authors.forename: T B
authors.initials: TB
authors.lastname: Tschopp
authors.forename: B J
authors.initials: BJ
authors.lastname: Weimann
mesh_terms: D000925:Anticoagulants; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors; D014312:Trisaccharides / Q000494:pharmacology*; D014462:Ultrafiltration
chemical_list: D000925:Anticoagulants; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D014312:Trisaccharides; C038505:trestatin; D006493:Heparin; D013917:Thrombin